NM_001042492.3(NF1):c.1260+2T>C AND Neurofibromatosis, type 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Oct 28, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001037303.9

Allele description [Variation Report for NM_001042492.3(NF1):c.1260+2T>C]

NM_001042492.3(NF1):c.1260+2T>C

Gene:

NF1:neurofibromin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_001042492.3(NF1):c.1260+2T>C

HGVS:

NC_000017.11:g.31201487T>C
NG_009018.1:g.111511T>C
NM_000267.3:c.1260+2T>C
NM_001042492.3:c.1260+2T>CMANE SELECT
NM_001128147.3:c.1260+2T>C
LRG_214t1:c.1260+2T>C
LRG_214:g.111511T>C
NC_000017.10:g.29528505T>C
NM_001042492.3:c.1260+2T>C

Links:

dbSNP: rs1555611110

NCBI 1000 Genomes Browser:

rs1555611110

Molecular consequence:

NM_000267.3:c.1260+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001042492.3:c.1260+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001128147.3:c.1260+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Neurofibromatosis, type 1 (NF1)
Synonyms:: NEUROFIBROMATOSIS, TYPE I; Recklinghausen's disease; Von Recklinghausen disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018975; MedGen: C0027831; Orphanet: 636; OMIM: 162200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200712	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10677298, 28492532
SCV001479143	Genome Diagnostics Laboratory, The Hospital for Sick Children	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002561648	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200712

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001479143

Genome Diagnostics Laboratory, The Hospital for Sick Children

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 26, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002561648

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 15, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Toward a survey of somatic mutation of the NF1 gene in benign neurofibromas of patients with neurofibromatosis type 1.

Eisenbarth I, Beyer K, Krone W, Assum G.

Am J Hum Genet. 2000 Feb;66(2):393-401.

PubMed [citation]

PMID:: 10677298
PMCID:: PMC1288091

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001200712.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in inclusion of 13 base pairs of intronic sequence and introduces a premature termination codon (PMID: 10677298). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 836228). Disruption of this splice site has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 10677298; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 11 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, The Hospital for Sick Children, SCV001479143.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002561648.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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